JPS6366160A - L-ascorbic acid retinoyl ester - Google Patents
L-ascorbic acid retinoyl esterInfo
- Publication number
- JPS6366160A JPS6366160A JP20998386A JP20998386A JPS6366160A JP S6366160 A JPS6366160 A JP S6366160A JP 20998386 A JP20998386 A JP 20998386A JP 20998386 A JP20998386 A JP 20998386A JP S6366160 A JPS6366160 A JP S6366160A
- Authority
- JP
- Japan
- Prior art keywords
- ascorbic acid
- ester
- retinoyl
- retinoic acid
- vitamin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 title claims abstract description 40
- 229960005070 ascorbic acid Drugs 0.000 title claims abstract description 19
- 239000002211 L-ascorbic acid Substances 0.000 title claims abstract description 17
- 235000000069 L-ascorbic acid Nutrition 0.000 title claims abstract description 17
- -1 L-ascorbic acid retinoyl ester Chemical class 0.000 title abstract description 5
- 150000002148 esters Chemical class 0.000 claims abstract description 5
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 abstract description 13
- 229930002330 retinoic acid Natural products 0.000 abstract description 13
- 229960001727 tretinoin Drugs 0.000 abstract description 13
- 238000006243 chemical reaction Methods 0.000 abstract description 8
- 230000000694 effects Effects 0.000 abstract description 8
- 102000001938 Plasminogen Activators Human genes 0.000 abstract description 6
- 108010001014 Plasminogen Activators Proteins 0.000 abstract description 6
- 229940127126 plasminogen activator Drugs 0.000 abstract description 6
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 abstract description 5
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 abstract description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 abstract description 4
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 abstract description 3
- 239000011719 vitamin A Substances 0.000 abstract description 3
- 235000019155 vitamin A Nutrition 0.000 abstract description 3
- 229940045997 vitamin a Drugs 0.000 abstract description 3
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 abstract description 2
- 229930003268 Vitamin C Natural products 0.000 abstract description 2
- 239000003957 anion exchange resin Substances 0.000 abstract description 2
- 239000002537 cosmetic Substances 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 abstract description 2
- 235000019154 vitamin C Nutrition 0.000 abstract description 2
- 239000011718 vitamin C Substances 0.000 abstract description 2
- 210000004204 blood vessel Anatomy 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 210000002889 endothelial cell Anatomy 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 239000002808 molecular sieve Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 210000003556 vascular endothelial cell Anatomy 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 2
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000003636 conditioned culture medium Substances 0.000 description 2
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 2
- 239000012679 serum free medium Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229960005356 urokinase Drugs 0.000 description 2
- GHPYJLCQYMAXGG-WCCKRBBISA-N (2R)-2-amino-3-(2-boronoethylsulfanyl)propanoic acid hydrochloride Chemical compound Cl.N[C@@H](CSCCB(O)O)C(O)=O GHPYJLCQYMAXGG-WCCKRBBISA-N 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102000013566 Plasminogen Human genes 0.000 description 1
- 108010051456 Plasminogen Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 230000003480 fibrinolytic effect Effects 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000007758 minimum essential medium Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 229960003471 retinol Drugs 0.000 description 1
- 235000020944 retinol Nutrition 0.000 description 1
- 239000011607 retinol Substances 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000003760 tallow Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Furan Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
（ビタミンＡ）とＬ−アスコルビン酸（ビタミンＣ）と
全併用すると、血管内皮細胞に作用してプラスミノーゲ
ンアクチペータの性成を促進し、線溶系全更進すること
を見い出した。[Detailed description of the invention] When used in combination with (vitamin A) and L-ascorbic acid (vitamin C), it acts on vascular endothelial cells, promotes the formation of plasminogen activator, and completely promotes the fibrinolytic system. I discovered that.
本発明は、レチノイン酸とＬ−アスコルビン撤とがエス
テル結合した新規物質全提供し、これが血管内皮細胞の
ゾラスミノーゲンアクチベータの活性の増大、レチノー
ルやレチノイン酸の親水性の増加、酸化による平安定性
の改善全目的とする。The present invention provides a novel substance in which retinoic acid and L-ascorbic acid are ester bonded, which increases the activity of zolasminogen activator in vascular endothelial cells, increases the hydrophilicity of retinol and retinoic acid, and reduces the stability due to oxidation. The overall purpose is to improve.
本発明は、Ｌ−アスコルビンＷＩＣＤ’６−０− レチ
ノイル、２，６７０−ジレチノイル又は２，５．６−〇
−トリレチノイルエステル誘導体である。The present invention is L-ascorbine WICD'6-0-retinoyl, 2,670-diretinoyl or 2,5.6-0-triretinoyl ester derivative.
Ｌ−アスコルビン酸は２．４．５及び６位に４個のヒド
ロキシ基をもつラクトンであり、レチノイン酸クロライ
ｒとの常法による反応により６位、２．６位及び２．５
．６位の酸エステルかえられるが、６位のモノ置換体が
一般的である。即ち、低温窒素気流下で塩酸生成をおさ
えながら、レチノイン酸と精製三塩化燐との反応により
レチノイン酸クロライドを得る。これ全緩和な条件下、
陰イオン交換樹脂あるいは低濃度ピリジ／の存在下でＬ
−アスコルビンＩＥト反応させ、反応液から抽出、更に
シリカゲルに□よるクロマトグラフィにより、目的のＬ
−アスコルビン酸のレチノイルエステルを得る。Ｌ−ア
スコルビン酸に対・するレチノイン酸り田ライドのモル
比を増加して反応させることにより、ジ置換体やトリ置
換体が得られる。L-ascorbic acid is a lactone with four hydroxy groups at the 2,4,5 and 6 positions, and it can be formed by reacting with retinoic acid chloride r by a conventional method.
．． Although the acid ester at the 6-position can be changed, a mono-substituted product at the 6-position is common. That is, retinoic acid chloride is obtained by reacting retinoic acid with purified phosphorus trichloride while suppressing the production of hydrochloric acid under a low-temperature nitrogen stream. Under all these mild conditions,
L in the presence of anion exchange resin or low concentration of pyridine
- React with ascorbine IE, extract from the reaction solution, and further chromatography using silica gel to obtain the desired L
- Obtaining the retinoyl ester of ascorbic acid. A di-substituted product or a tri-substituted product can be obtained by increasing the molar ratio of retinoic acid aritalide to L-ascorbic acid and causing the reaction.
本発明のし一アスコルビン酸のレチノイルエステルは、
それぞれ全単用又は併用した場合に比べてさらに高いプ
ラスミノーゲンアクチベータ活性を示す。またビタミン
Ａ作用及びビジ９フ０作川音有するため医薬、食品、化
粧品として有用である。The retinoyl ester of ascorbic acid of the present invention is
Each shows higher plasminogen activator activity than when used alone or in combination. In addition, it is useful as a medicine, food, and cosmetic because it has vitamin A action and biji9f0sakukawaon.
実施例
１） レチノイン酸クロライドの合成
１２のレチノイン酸’１１００＋＋＋ｌのトルエンに溶
解し、モレキュラーシーブ３Ａ全添加して一夜窒素存在
下で乾燥した。モレキュラーシーブを傾斜法によって除
去した後、これに水冷下及び窒素気流下に９５０μ、ｅ
の精製三塩化燐全加え、０℃で４時間反応させた。反応
終了後、低温遮光下で減圧濃縮し、レチノイン酸クロラ
イド１、ｏ５ｙｖ得た。これを乾燥ツメチルホルムアミ
ド１５ｍＡ’に溶解した。Example 1) Synthesis of retinoic acid chloride Retinoic acid '1100+++1 of 12 was dissolved in toluene, all of the molecular sieve 3A was added thereto, and the mixture was dried overnight in the presence of nitrogen. After removing the molecular sieve by a decanting method, it was heated to 950μ, e.g. under water cooling and nitrogen flow.
All of the purified phosphorus trichloride was added thereto, and the mixture was reacted at 0°C for 4 hours. After the reaction was completed, the mixture was concentrated under reduced pressure under low temperature light shielding to obtain retinoic acid chloride 1, o5yv. This was dissolved in 15 mA' of dry trimethylformamide.
２） Ｌ−アスコルビン酸の６−０−レチノイルエス
テルの合成
１．７６９のＬ−アスコルビン酸を２５ｍＡ！のジメチ
ルホルムアミドに溶解し、モレキュラーシーブ３Ａ ２
２を加えて遮光下で一夜乾燥した。2) Synthesis of 6-0-retinoyl ester of L-ascorbic acid 1.769 L-ascorbic acid at 25 mA! Molecular sieve 3A 2
2 was added and dried overnight in the dark.
モレキュラーシーブを除いたのち、２１の乾燥アンバー
ライトＩＲＡ ４００ （ＯＨ置換体）を加え、レチノ
イン酸りロライド溶液１５ｍ／７１滴下した。After removing the molecular sieve, 21 dry Amberlite IRA 400 (OH substituted product) was added, and 15 m/71 of a retinoic acid loride solution was added dropwise.
さらに遮光下３５℃で攪拌しながら５時間反応させた。Further, the reaction was allowed to proceed for 5 hours while stirring at 35°C in the dark.
反応終了後、低温減圧濃縮で溶媒全除去したのち、２５
０ｍ１のメタノール：クロロホルム＝１＝１に溶解、５
Ｍ食塩水で洗浄したのち、２５０ ｍｌのｎ−ヘキサン
ケ加え、４℃に冷却した。上層全除去したのち下層全減
圧濃縮し、粗生成物１．０４ｆ’ｉ得た。これ全シリカ
ゲルによるクロマトグラフィ（エタノール；クロロホル
ム−１：４）により２回精製し、目的のＬ−アスコルビ
ン酸の６−〇−レチノイルエステル２４０■を得た。
ｍｐ ： ９７℃
精精製品はクロロホルム中で３５０ｎｍＫ吸収極犬全有
し、その吸光係数は４５０００である。After the reaction was completed, all the solvent was removed by concentration under reduced pressure at low temperature, and 25% of the solvent was removed.
Dissolved in 0ml methanol:chloroform=1=1, 5
After washing with M salt solution, 250 ml of n-hexanke was added and cooled to 4°C. After removing the entire upper layer, the entire lower layer was concentrated under reduced pressure to obtain 1.04 f'i of crude product. This was purified twice by chromatography using all-silica gel (ethanol:chloroform-1:4) to obtain 240 μl of the desired 6-0-retinoyl ester of L-ascorbic acid.
mp: 97°C The purified product has a total absorption of 350 nm K in chloroform, and its extinction coefficient is 45,000.
３）血管内皮細胞の培養
生類動脈より採取した血管内皮細胞金、５５ｃＩｒＬ２
ヘトリ皿上、１ｏｑｂ牛脂児血清、ペニシリン（５０Ｕ
／ｍｌ ） およびストレプトマイシン（５０ｍｃｇ
／ｍｌ ） ｆ含む最小必須培地中で継代培養した。3) Culture of vascular endothelial cells Vascular endothelial cells collected from biological arteries Gold, 55cIrL2
On a helium plate, 1 ozb tallow serum, penicillin (50 U
/ml) and streptomycin (50 mcg
/ml) and subcultured in minimum essential medium containing f.
１５回植継ぎをおこなった後に、ベトリ皿の細胞を１２
枚の別の９ｃＩＩＬ２−！！トリ皿に植継いだ。３日間
上記の条件で培養を行い、細胞ｔコンフルーエ／トにし
たのちに、培養液中に、レチノイン［、Ｌ−アスコルビ
ン酸及びＬ−アスコルビン酸の６−レチノイルエステル
の各々を終濃度が１０μＭとなるように添加し、５［１
間培養をつづけた。（実験は対照も含め、３枚ずつ行っ
た）Ｌ−アスコルビン酸は２ ｍＭエタノール溶液金調
裂し、細胞培養液２ＣＣに１０１１７ずつ加えた。培養
液のエタノール濃度はすべて０．５％に統一した。After 15 subcultures, the cells in the Vetri dish were transferred to 12
Another 9cIIL2-! ! It was subcultured into a bird dish. After culturing under the above conditions for 3 days and making the cells confluent, each of retinoin [, L-ascorbic acid and 6-retinoyl ester of L-ascorbic acid] was added to the culture medium at a final concentration of 10 μM. Add so that 5 [1
Interculture was continued. (The experiment was carried out in triplicate, including a control.) L-ascorbic acid was diluted with a 2 mM ethanol solution and added in 10117 portions to 2CC of cell culture medium. The ethanol concentration of all culture solutions was unified at 0.5%.
４）プラスミノーゲンアクチベータ活性の測定各種条件
で、５日間培養した細胞勿無血清培地で洗ったのちに、
２ｍｌの無血清培地で８時間培養し、それぞれのコンデ
ィションメディア全得た。２−３ミクロンのフィブリン
粒子からなる懸濁液を調製し、懸濁液７００μｐにプラ
スミノゲン溶液１００μ！とコンディションメディアも
しくは既知濃度のウロキナーゼ溶液２００μ！を加え、
３７℃で培養した。経時的に反応系の濁度を計ることに
より、各種条件で培養した細胞から得たコンディション
メディア中のプラスミノーゲンアクチペータ活性を測定
し、ウロキナーゼ国際単位に換算して表した。4) Measurement of plasminogen activator activity Cells cultured under various conditions for 5 days were washed with serum-free medium.
The cells were cultured in 2 ml of serum-free medium for 8 hours, and each conditioned medium was completely obtained. A suspension consisting of 2-3 micron fibrin particles was prepared, and 700 μp of the suspension was mixed with 100 μp of the plasminogen solution. and condition media or urokinase solution of known concentration 200μ! Add
Cultured at 37°C. By measuring the turbidity of the reaction system over time, the plasminogen activator activity in conditioned media obtained from cells cultured under various conditions was measured and expressed in terms of urokinase international units.
結果は表１に示すように、細胞外に産生されたプラスミ
ノーゲンアクチペータの活性は、対照に比べてレチノイ
ン酸で２．６倍、Ｌ−アスコルビン酸で１，５倍、さら
にＬ−アスコルビン酸の６−レチノイルエステルで１３
．８倍にそれぞれ増加した。As shown in Table 1, the activity of extracellularly produced plasminogen activator was 2.6 times higher with retinoic acid, 1.5 times higher with L-ascorbic acid, and 1.5 times higher with L-ascorbic acid compared to the control. 13 with 6-retinoyl ester of acid
．． Each increased 8 times.
表１Table 1
Claims (1)
−ジレチノイル又は２，５，６−Ｏ−トリレチノイルエ
ステル誘導体。6-O-retinoyl, 2,6-O of L-ascorbic acid
- diretinoyl or 2,5,6-O-triretinoyl ester derivative.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20998386A JPH0780865B2 (en) | 1986-09-06 | 1986-09-06 | L-Ascorbic acid retinoyl ester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20998386A JPH0780865B2 (en) | 1986-09-06 | 1986-09-06 | L-Ascorbic acid retinoyl ester |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6366160A true JPS6366160A (en) | 1988-03-24 |
| JPH0780865B2 JPH0780865B2 (en) | 1995-08-30 |
Family
ID=16581914
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP20998386A Expired - Lifetime JPH0780865B2 (en) | 1986-09-06 | 1986-09-06 | L-Ascorbic acid retinoyl ester |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0780865B2 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5189057A (en) * | 1990-07-20 | 1993-02-23 | Takeda Chemical Industries, Ltd. | Saccharoascorbic acid derivatives |
| US5605933A (en) * | 1993-12-15 | 1997-02-25 | Avon Products, Inc. | Retinoid conjugate compounds and methods for treating of skin aging |
| JP2010506830A (en) * | 2006-10-12 | 2010-03-04 | コスモル カンパニー リミテッド | Method for producing crystalline 3-O-substituted ascorbic acid |
| WO2015073769A1 (en) | 2013-11-15 | 2015-05-21 | Us Cosmeceutechs Llc | Retinoid double conjugate compounds, compositions thereof, and methods for treating of skin conditions |
-
1986
- 1986-09-06 JP JP20998386A patent/JPH0780865B2/en not_active Expired - Lifetime
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5189057A (en) * | 1990-07-20 | 1993-02-23 | Takeda Chemical Industries, Ltd. | Saccharoascorbic acid derivatives |
| US5605933A (en) * | 1993-12-15 | 1997-02-25 | Avon Products, Inc. | Retinoid conjugate compounds and methods for treating of skin aging |
| US5863942A (en) * | 1993-12-15 | 1999-01-26 | Avon Products, Inc. | Retinoid conjugate compounds useful for the treatment of aging skin |
| JP2010506830A (en) * | 2006-10-12 | 2010-03-04 | コスモル カンパニー リミテッド | Method for producing crystalline 3-O-substituted ascorbic acid |
| WO2015073769A1 (en) | 2013-11-15 | 2015-05-21 | Us Cosmeceutechs Llc | Retinoid double conjugate compounds, compositions thereof, and methods for treating of skin conditions |
| US10123960B2 (en) | 2013-11-15 | 2018-11-13 | Pcr Technology Holdings, Lc | Methods for treating of skin conditions with retinoid double conjugate compounds |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0780865B2 (en) | 1995-08-30 |
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